The ethics of research involving animals - Nuffield Council on ...

T h e e t h i c s o f r e s e a r c h i n v o l v i n g a n i m a l s
For complete replacement <strong>of</strong> <strong>animals</strong>, an alternative method should not require any
animal-derived biological material. Examples <strong>of</strong> such methods or approaches include the
use <strong>of</strong> predictions based on the physical and chemical properties <strong>of</strong> molecules,
mathematical and computer studies <strong>of</strong> biological processes, analysis <strong>of</strong> epidemiological
data, <strong>research</strong> <strong>involving</strong> human participants or <strong>research</strong> on isolated human cells and
tissues in culture (see Box 11.1). However, many methods considered as Replacements also
use some biological material obtained from living or humanely killed <strong>animals</strong>. <strong>The</strong>se
include <strong>research</strong> on cells and tissues derived from living or humanely killed <strong>animals</strong> for
culture in vitro and animal-derived growth supplements such as serum derived from fetal
or newborn calves. <strong>The</strong>se methods can be called incomplete Replacements. 4
Box 11.1: Complete and incomplete
replacements
Computer studies and in vitro methods
Mathematical and computer modelling studies (in
silico techniques) comprise a variety <strong>of</strong> approaches.
<strong>The</strong>y include the prediction <strong>of</strong> the biological activity <strong>of</strong>
substances, and the modelling <strong>of</strong> biochemical,
physiological, pharmacological, toxicological and
behavioural systems and processes.* In vitro
techniques are also varied, increasing in complexity
from subcellular (cell-free) fractions, through primary
cells and cell lines grown in liquid suspension, and
three-dimensional cultures, to tissue slices or
fragments and even whole perfused organs, all
consisting <strong>of</strong> cells or tissues derived from <strong>animals</strong> or
humans.† Examples <strong>of</strong> techniques that involve cells,
tissues or organs from <strong>animals</strong> that have been killed
humanely include: the use <strong>of</strong> guinea pig skin to
provide information that would previously have been
obtained from tests on the skin <strong>of</strong> living <strong>animals</strong>, or
the use <strong>of</strong> primary cell cultures to replace neonatal
mice as a virus isolation or assay system.
Human studies
In many types <strong>of</strong> biomedical and toxicological
<strong>research</strong>, <strong>animals</strong> are used because ethical
considerations preclude conducting the experiments
on humans. However, a number <strong>of</strong> approaches have
been suggested which, in some cases, might replace
the use <strong>of</strong> <strong>animals</strong> with studies on humans. <strong>The</strong>se
include non-invasive brain scanning to replace some
experiments on primates,‡ and studies on ultra-lowdose
ADME metabolism in human volunteers in the
early stages <strong>of</strong> selection for potential medicines.∫
Human tissue samples can be used both for direct
examination (e.g. histopathology) and in cell culture
and other in vitro techniques.**
* Using, for example, molecular modelling and the
development <strong>of</strong> quantitative structure-activity
relationships; see Combes RD and Judson P (1995) <strong>The</strong>
use <strong>of</strong> artificial intelligence systems for predicting
toxicity Pest Sci 45:179–94; Combes RD and Rodford R
(2003) <strong>The</strong> use <strong>of</strong> expert systems for toxicity prediction –
illustrated with reference to the DEREK program, in
Modelling Environmental Fate and Toxicity Cronin M and
Livingstone D (Editors) (London: Taylor & Francis);
Assessing the cumulative effect <strong>of</strong> mutations: Kirkwood
TB & Proctor CJ (2003) Somatic mutations and ageing in
silico Mech Ageing Dev 124:85–92.
† <strong>The</strong> European Collection <strong>of</strong> Cell Cultures (ECACC)
operates a cell bank <strong>of</strong> peripheral lymphocytes from
approximately 40,000 donors. Forty percent are in the
form <strong>of</strong> lymphoblastoid cell lines representing around
450 genetic disorders. <strong>The</strong>se lines are useful for the
analysis <strong>of</strong> the role <strong>of</strong> genes in disorders that have a
genetic component, for example cardiovascular diseases,
Alzheimer’s disease or depression.
‡ Langley G, Harding G, Hawkins P, et al. (2000) Volunteer
studies replacing animal experiments in brain <strong>research</strong>
Alternat Lab Anim 28: 315–31.
∫
In this type <strong>of</strong> <strong>research</strong>, the absorption, distribution,
metabolisation and excretion (ADME) <strong>of</strong> new medicines is
assessed by measuring the effects <strong>of</strong> administering
extremely low doses <strong>of</strong> candidate compounds.
Extrapolations are then made concerning the effects <strong>of</strong>
higher doses. <strong>The</strong> approach is at the early stages <strong>of</strong>
development and is not yet suited to replace the use <strong>of</strong>
<strong>animals</strong> in pharmaceutical <strong>research</strong>. Combes RD, Berridge
T, Connelly J et al. (2003) Early microdose drug studies in
human volunteers can minimise animal testing.
Proceedings <strong>of</strong> a workshop organised by volunteers in
<strong>research</strong> and testing Eur J Pharm Sci 19: 1–11.
** Access to patients and issues <strong>of</strong> consent are critical factors
in the feasibility <strong>of</strong> human studies, see paragraph 11.26.
CHAPTER 11 REPLACEMENTS
11.7 Tests using invertebrates, or early developmental stages <strong>of</strong> vertebrates (i.e. before they
reach the point at which their use in experiments and other scientific procedures is
regulated), are also sometimes described as Replacements, even though they do not
replace <strong>animals</strong> per se. For example, the horseshoe crab (Limulus) can be used to replace
4 Although this practice does not replace the use <strong>of</strong> <strong>animals</strong> per se, it replaces the carrying out <strong>of</strong> procedures on living <strong>animals</strong>.
Sacrificing the life <strong>of</strong> one animal can save the lives <strong>of</strong> many other <strong>animals</strong>, as its organs and tissues can be used in many
different experiments. <strong>The</strong> humane killing <strong>of</strong> an animal carried out according to methods prescribed in Schedule 1 <strong>of</strong> the A(SP)A
is not counted as a procedure.
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